Category: Ghostwriting

Seroxat/Paxil Study 329: Nobody Pinned Anything on Us


http://brodyhooked.blogspot.ie/2012/07/inside-paxil-study-329-courtesy-justice.htmlhttp://brodyhooked.blogspot.ie/2012/07/inside-paxil-study-329-courtesy-justice.html

“…Inside Paxil Study 329, Courtesy the Justice Department

I’ve previously discussed the now-infamous Study 329, which took discouraging data on the efficacy and safety of paroxetine (Paxil) in kids and spun it into an article claiming excellent results:
http://brodyhooked.blogspot.com/2011/11/will-brown-university-investigate.html

Thanks to the U.S. Justice Dept. complaint in the suit recently settled by GlaxoSmithKline for a record $3B: http://www.justice.gov/opa/documents/gsk/us-complaint.pdf
–we can follow the history of this study in more detail, based on the internal GSK documents discovered during the proceedings, and see just how the data were manipulated for marketing purposes.

Study 329, directed by Dr. Martin Keller of Brown University, was one of 3 clinical studies in children and adolescents that were all interpreted by GSK scientists between August and October, 1998 to be discouraging. Study 329’s protocol specified two primary endpoints, and on neither measure did Paxil do better than placebo. The study also logged in 11 serious adverse reactions to Paxil, much more than in the placebo group, including 5 with agitated or suicidal behavior, the major risk for which eventually the FDA issued a black-box warning for the SSRI class of antidepressants…”

 

http://davidhealy.org/study-329-response-from-the-authors/#comment-44667

 

What exactly did Martin Keller mean when he said that ‘nobody ever pinned anything on us’? (in regards to his involvement in the Paroxetine-Paxil/Seroxat Study 329).

Interesting ‘choice of words’ methinks…

 


 

Study 329: Nobody Pinned Anything on Us

March, 31, 2016 | 2 Comments

 

 

The Flaws In Ben Goldacre’s ‘Evidence Based Medicine’ Transparency Agenda


Ben Goldacre

Ben Goldacre has become somewhat of a ‘key opinion leader’ in the arena of science and pharmaceutical practices. His approachable persona, backed by his best selling books and much-read Guardian column, has made him into something of a celebrity in the UK. He has done TED talks and even appeared in Stephen Fry’s QI TV show. He has over 250,000 twitter followers and many more fans who comment on his bad science blog. He is asked his opinion on a range of different issues, from health care to public policy. When Goldacre expresses his opinion- people listen…he’s quite popular.

Perhaps this is why GSK are so keen to be associated with him?

Ben has been running a campaign for access to all clinical trial data, through his Alltrials organization, and he’s even managed to get GSK to sign up to it. Although it sounds fairly promising (if you believe the PR sound-bites) ,GSK haven’t actually delivered on anything yet, but they have made some half-baked promises about access to their clinical trial data in the coming years (how, when, or in what form- this transparency will be- is still very vague and unclear). Of course transparency itself is all well and good (and indeed I applaud Ben for such a noble aspiration)  however, what use is the clinical trial data (or evidence based medicine) when it is manufactured, analysed and selectively interpreted by the drug makers themselves? (and of course there is also the possibility of destroying the unfavorable data altogether and never letting it see the light of day- if it no longer exists – you can’t be expected to show it). It’s issues like those mentioned, as well as many others, which highlights the impotence of Ben Goldacre’s quest for transparency from the industry. Nonetheless, the good PR generated for pharma for appearing to usher in an era of transparency earns companies like GSK many ethical brownie points (which are undoubtedly invaluable in a highly competitive market with so much public mistrust and cynicism towards it from the general public).

Ben’s argument rests upon the premise that randomized clinical trial data (RTC’s) presented by the pharmaceutical industry is the gold standard of assessing risks and benefits of medications. He calls for access to all clinical trials because he claims that the industry suppresses the negative trials and promotes the positive ones. He is correct here- this is what industry does and this is of course unethical and wrong, and it’s been going on for decades. Of course all data should be published, and it’s amazing how the industry have gotten away with this sham for so long.

Nevertheless, this focus on suppression of negative trial data is really a bit of a red herring, because not only do companies like GSK hide negative data about their drugs, but they also have the power to manipulate the trials both in their design and interpretation- in order to generate an appearance of efficacy and safety. They control the whole process, they create the data, they design the methods and they interpret the results, therefore it is the process itself which is corruptible. This is far from a gold standard, and many dangerous medications still make it to market- despite regulatory approval based on clinical trials! (Vioxx, Avandia, Seroxat, Zyprexa … to name but a few of the recent past). 

Dr David Healy explains how they do this in an interview here:

“There are a few ways that RCTs can hide effects. First, the process doesn’t encourage anyone to look closely at particular things that happen on a drug—the focus is instead on the group and on average effects. That’s true of all trials. In company trials there are more specific problems like miscoding, where suicidality becomes “nausea” or “emotional lability” or even “treatment non-responsiveness.”

There is also the problem of mislocation—patients on placebo end up being given problems they never had—and of nonexistent patients, who don’t of course have adverse events.

Beyond that, there are more sophisticated tricks that companies can and do play—such as claiming that increased rates of a problem on a drug are not really evidence of an increase in rates if the data are not statistically significant. In this way, companies have hidden many more heart attacks on Vioxx and Avandia or suicidal acts on SSRIs than have been hidden by miscoding or mislocation.

Isn’t what you’re describing tantamount to

fraud? I’m all in favor of clinical trials—if done right, wouldn’t they give us the correct answer?

Actually no, when it comes to adverse events, trials almost never get the right answer.

Let’s assume in a trial that we have 3,000 depressed patients on Paxil who had 10 suicidal acts and 1,750 on placebo who had 0 suicidal acts. Paxil clearly causes suicidal acts here. Now let’s take 200 depressivepersonality disorder patients on Paxil who have 30 suicidal acts and 200 depressive personality disorder patients on placebo who have 25 suicidal acts—again, that’s an increased rate of suicidal acts on Paxil. But add these two increases together and you end up with a reduced rate of suicidal acts on the SSRI compared to placebo—40 suicidal acts in 3,200 patients is less than 25 in 1,950.

Hey presto—problem gone. Exactly the same thing can happen in every clinical trial where we don’t fully understand the condition we’re treating—which is, frankly, most conditions from back pain to diabetes to psychosis. We mix patients who superficially appear the same but who in fact have different conditions.

That is just one trick that no-one ever mentions—I’ve laid out several more on davidhealy.org.

Is there any way to overcome such tricks and masking problems?

Yes, actually, there is. One way is to do trials in healthy volunteers—these are the true drug trials. Companies do these but rarely publish them. There’s no register of these trials and no data are made available, though there’s no issue of clinical confidentiality involved. Given that these trials tell us so much—10 years before Zoloft came on the market, for instance, they indicated that the drug made healthy volunteers suicidal—it’s a huge scandal that these data in particular are buried.”

Another problem is- although clinical trial data can be useful, most clinical trials of psychiatric drugs are merely 6 to 12 weeks in duration– they are way too short to assess risks. Short trials give little (or virtually no) indication of long term affects for a lot of drugs. In the case of psychiatric drugs, it can take some weeks (and even months) for the drug to fully metabolize in the body. It can take even longer for the body to develop tolerance and dependence. Each individual is different therefore they will have a different reaction and the side effects will vary. It is often – only after a few years on the drug -that people realize that they are having serious side effects. In the case of Seroxat – it seems the longer the individual remains on Seroxat the greater the risks increase, and the harder it is to come off it. Problems like withdrawal, addiction, and issues of toxicity, are often only discovered long after the drug is approved thus only after many millions of people have been taking it for a few years.

GSK have altered the Seroxat PIL so many times over the years that if you compare the first PIL from 1991 to the ones from the last few years they are barely recognizable as so many side effects (and rates of occurrence of side effects) have been added.

See here: http://seroxatsecrets.wordpress.com/2009/12/30/the-seroxat-paxil-pil-over-the-years-ch-ch-ch-changes/

Corruption of clinical trials and falsification of data does happen, therefore in trusting in clinical trials, we have to also trust that the people involved in the trials are ethical. Seroxat Secret has highlighted this problem on his blog : see here

GlaxoSmithKline is the subject of more bad publicity after a researcher was allegedly found to have falsified data in trials about Paxil. Meanwhile, the drug maker faces lawsuits alleging newborns suffered Paxil Birth defects when they were exposed to Paxil prior to birth.

The psychiatrist who reportedly falsified clinical data, Dr. Maria Carmen Palazzo, was a clinical investigator on studies conducted by SmithKline Beecham (doing business as GlaxoSmithKline). According to CNBC on 8/20/10, Palazzo has now pleaded guilty to 15 counts of failing to prepare and maintain records with the intent to defraud and mislead.

Palazzo reportedly included children in a study that involved diagnoses the children did not have. Prosecutors claimed that Palazzo also reported symptoms that her study subjects did not exhibit. She was sentenced to 13 months in prison, which she is serving at the same time as an 87-month term for healthcare fraud.

According to BNET (08/19/10), Palazzo was charged after the Federal Drug Administration (FDA) accused her of enrolling children in studies of obsessive-compulsive disorder and major depressive disorder even though the children she studied did not have the proper diagnosis for inclusion in the study.

Paxil now carries a black box warning about the risk of suicide in children. It also carries a warning about the risk of birth defects in babies exposed to the antidepressant prior to birth.

Remember, Glaxo has a track record of hiding negative clinical trial data that would knock sales of its drugs – the story of Seroxat and Study 329 is truly shocking.

Read more about Seroxat here:
More on Paxil and suicide – “Glaxo was aware of this risk, and hid it”

and here:

Glaxo fails in its responsibility to patients and it hid Seroxat data – it’s official

And what happens in the UK when the MHRA  undertakes a criminal investigation into Glaxo and the withholding of clinical trial data?… and finds Glaxo guilty…?

The answer is nothing happened to Glaxo – nothing at all.”

Even when some companies get a negative result from a clinical trial, they can hire ghost writers to fluff up the results and make it appear that the trial was a positive one. This happened with Seroxat study 329 and tragically many children and young people were prescribed an extremely harmful drug because of it. See here :

The court documents released as a result of one of the lawsuits in October 2008 indicated that GSK “and/or researchers may have suppressed or obscured suicide risk data during clinical trials” of Seroxat. One of the investigators, “Charles Nemeroff, former chairman of the Department of Psychiatry at Emory University, was the first big name ′outed′. In early October 2008, Nemeroff stepped down as department chair amid revelations that he had received over $960,000 from GSK in 2006, yet reported less than $35,000 to the school. Subsequent investigations revealed payments totaling more than $2.5 million from drug companies between 2000 and 2006, yet only a fraction was disclosed”.

Disclosure of all clinical trial data is a step in the right direction, and it is a major issue which needs to be addressed, and I sincerely applaud Ben Goldacre for highlighting what he believes to be an important issue, but the problems of drug regulation, broken ethics, undue influence of industry on academia, and corruption in the industry itself, also need to be addressed if we are to avoid patient deaths from defective and dangerous drugs which should not have been approved.

Companies like GSK operate above the law in the UK, they are virtually untouchable. Perhaps if Ben Goldacre was to concentrate his efforts on attaining  justice for those harmed by medications such as Seroxat and Avandia, GSK might begin to manifest a sense of real atonement and change, or at the very least they might say sorry. It is only through the courts that GSK would be forced to reveal and disclose hidden information and data. But again, unfortunately, in the UK, pharma-litigation cases are usually squashed before they get to trial. The establishment have a vested interest in protecting GSK, they are a major UK cash-cow… and despite an utterly dire track record of  harm to consumers, corruption, lies and fraud for decades, they even have the UK prime minister defending them. What hope is there, for damaged patients from GSK drugs, in a situation like that? What hope is there for justice?

Ben Says:

“I don’t think GSK will be the only company to sign up. I think we’re going to enter a very interesting era where potentially the market is differentiated by ethical companies who’ve made a commitment to sharing all their trial results, and unethical companies who are still aggressively defending their ability to withhold information from doctors and patients.”

I agree with Ben here, that era is now upon us, and GSK have gained more positive publicity than any other company for basically promising to be more ethical.

Essentially they have positioned themselves quite strongly within this frame because it is in their economic interest to appear to want to be an ethical company.

They haven’t actually delivered on any of this yet and I sincerely hope that they do, but I have a feeling that they will find a way around it while still seeming to be the good guys.(they are a clever bunch). But for the time being, they are certainly generating a lot of column inches full of positive praise because of all this (such great PR for them).

Furthermore, ironically, GSK have said they will only give access to data for drugs released after the company merger (after 2000) therefore the hidden  trials of the most dangerous and infamous of their drugs- Seroxat (1991) and Avandia (1999)- will likely never see the light of day…

How convenient for them

How tragic for the families of the dead and the damaged..

As David Healy said:

“Now it is unfair to say if Ben Goldacre didn’t exist perhaps Andrew Witty would have to invent him?”

Indeed, that would be (fairly) unfair..
However, I’m not the only one to express such cynicism about GSK and their promises of transparency, see the following comments from this article about GSK’s promises..

“He’d like to see all of the clinical study reports ever completed brought out of “dry storage archive…and everywhere else that people stack their old, crinkly, yellow paperwork” and made publicly available — ideally on his new website, AllTrials.net, which recently signed on GlaxoSmithKline (GSK) to release every study the company has ever done.  (Mistake —  anything after the merger (2000)… NOT every study the company has ever done

Beverly Richards-Smith, PhD”02/24/13

“How will Dr. Goldacre or AllTrials.net ensure that GSK, or any pharmaceutical company that registers in the future, actually provides all its “old, crinkly, yellow paperwork?” It will remain up to the corporations to determine what trial results are “located” and made public. I suspect that results from older trials for drugs that have been superseded by newer products will be provided in their entirety when possible, but those for drugs that are sources of significant current corporate income will be cherry-picked to exclude negative data of a sort that might reduce the drug’s prescription rate. The threat of lawsuits resulting from lethal or severe side effects is less likely to keep a study off the Web site, as Big Pharma regards lawsuit settlements, even on what appears to outsiders to be a large scale, simply as part of the cost of doing business. If the side effects can be “justified” by the supposed benefits of the drug – e.g., 1-2% risk of diabetes vs. the claims of protection from heart attacks for statin drugs – then prescription numbers won’t be affected..”

Our “evidence-based” medicine is only as good as the “evidence”. So if the “evidence” is bad—meaning poorly constructed studies, badly interpreted or just plain fraudulent data—then so is the recommendations, policies and practices developed using that “evidence”..

jmz, MD

02/25/13

“What a waste of time, as Dr. Goldacre, like many before him, think the data should be on his site where evidently he can judge its importance. What a crock. As far as I know, GSK has already reneged on their promise. They never will release all their data and others will not also. The same is true for almost all funded research. Not all data is released and even if it were released, it would likely not be possible to analyze it because many internal information items would be missing. It’s a pipedream and please tell me how “evidence-based medicine” would improve. It sounds to me that Dr. Goldacre is after fame that is not his due..”

Bay Area MD

03/02/13

“The application of evidence-based medicine is often misguided and indiscriminately applied to a larger population than what the studies often show with few if any postmarketing studies showing the true insignificant benefits and/or greater harm created. The withholding of negative data is unethical and prevents real peer review. Evidence based medicine is quite a disappointment..”

 

Seroxat Trebles The Risk Of Suicide For Under 18’s


 

What’s the difference for over 18’s? Over 21’s? Under 25’s? Adults?How suicidal does it make those age-groups?

What is GSK still hiding from the public all these years later?

Maybe in 2014 we’ll find out?